Krill oil supplementation's effect on school grades in typically developing adolescents.

Long-chain polyunsaturated fatty acids (LCPUFA) are important for brain development and functioning and with that, possibly school performance. Several cross-sectional studies have shown significant positive associations between fish consumption, an important source of LCPUFA and school grades in adolescents. The effect of LCPUFA supplementation on school grades in adolescents has not been investigated yet. The goal of the current study was to investigate (I) the associations between the Omega-3 Index (O3I) at baseline and after 12 months respectively and school grades and (II) the effect of one year krill oil supplementation (source of LCPUFA) on school grades in adolescents with a low O3I at baseline. A double-blind randomised placebo-controlled trial with repeated measurements was executed. Participants received either 400 mg eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) per day for the first three months in Cohort 1 and the nine months thereafter 800 mg EPA + DHA per day, Cohort 2 started immediately with 800 mg EPA + DHA per day,or a placebo. The O3I was monitored with a finger prick at baseline, three, six and twelve months. Subject grades for English, Dutch and math were collected, a standardised mathematics test was executed at baseline and at 12 months. Data was analysed with (I) explorative linear regressions to investigate associations at baseline and follow-up and (II) mixed model analyses separately for each of the subject grades and the standardised mathematics test to investigate the effect of supplementation after 12 months. The krill oil group had a small significant increase in the mean O3I at all time points. However, very few participants achieved the intended target O3I range of 8-11%. At baseline a significant association between baseline O3I and English grade was show, additionally a trend for an association with Dutch grade was shown. After 12 months no significant associations were found. Additionally, there was no significant effect of krill oil supplementation on subject grades or standardised mathematics test score. In this study, no significant effect of krill oil supplementation on subject grades or standardised mathematics test performance was found. However, as many participants dropped out and/or were non-adherent, results should be interpreted with caution.

Impact of intravenous fish oil on omega-3 fatty acids and their derived lipid metabolites in patients with parenteral nutrition.

BACKGROUND: Long-term parenteral nutrition (PN) can lead to intestinal failure-associated liver disease (IFALD). Omega-3 (n-3) polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were shown to prevent IFALD. EPA-derived and DHA-derived oxylipins could contribute to this protective effect. METHODS: We analyzed the effect of parenteral fish oil on oxylipins in patients with chronic intestinal failure receiving PN (n = 8). Patients first received no fish oil for 8 weeks and then switched to PN with 25% of fat as fish oil for another 8 weeks. Fatty acid profiles of red blood cells, PUFA-derived oxylipins generated by cyclooxygenase, lipoxygenase (LOX), and cytochrome P450 (CYP) pathways, inflammatory markers, and liver function were assessed before and during fish-oil PN. RESULTS: EPA plus DHA in erythrocytes (the Omega-3 Index) was high with a median of 11.96% at baseline and decreased to 9.57% without fish oil in PN. Addition of fish oil in PN increased the median Omega-3-Index to 12.75%. EPA-derived and DHA-derived CYP-dependent and LOX-dependent metabolites increased significantly with fish oil in PN, with less pronounced changes in arachidonic acid and its oxylipins. There were no significant changes of inflammation and liver function parameters. CONCLUSIONS: This study shows that fish oil-containing PN leads to primarily CYP- and LOX-dependent n-3 PUFA-derived inflammation-dampening oxylipins arising from EPA and DHA. Within this short (16-week) study, there were no significant changes in inflammation and clinical readout parameters.

Cardiac Rehabilitation in German Speaking Countries of Europe-Evidence-Based Guidelines from Germany, Austria and Switzerland LLKardReha-DACH-Part 2.

BACKGROUND: Scientific guidelines have been developed to update and harmonize exercise based cardiac rehabilitation (ebCR) in German speaking countries. Key recommendations for ebCR indications have recently been published in part 1 of this journal. The present part 2 updates the evidence with respect to contents and delivery of ebCR in clinical practice, focusing on exercise training (ET), psychological interventions (PI), patient education (PE). In addition, special patients' groups and new developments, such as telemedical (Tele) or home-based ebCR, are discussed as well. METHODS: Generation of evidence and search of literature have been described in part 1. RESULTS: Well documented evidence confirms the prognostic significance of ET in patients with coronary artery disease. Positive clinical effects of ET are described in patients with congestive heart failure, heart valve surgery or intervention, adults with congenital heart disease, and peripheral arterial disease. Specific recommendations for risk stratification and adequate exercise prescription for continuous-, interval-, and strength training are given in detail. PI when added to ebCR did not show significant positive effects in general. There was a positive trend towards reduction in depressive symptoms for "distress management" and "lifestyle changes". PE is able to increase patients' knowledge and motivation, as well as behavior changes, regarding physical activity, dietary habits, and smoking cessation. The evidence for distinct ebCR programs in special patients' groups is less clear. Studies on Tele-CR predominantly included low-risk patients. Hence, it is questionable, whether clinical results derived from studies in conventional ebCR may be transferred to Tele-CR. CONCLUSIONS: ET is the cornerstone of ebCR. Additional PI should be included, adjusted to the needs of the individual patient. PE is able to promote patients self-management, empowerment, and motivation. Diversity-sensitive structures should be established to interact with the needs of special patient groups and gender issues. Tele-CR should be further investigated as a valuable tool to implement ebCR more widely and effectively.

Prooxidative chain transfer activity by thiol groups in biological systems.

Cysteine is arguably the best-studied biological amino acid, whose thiol group frequently participates in catalysis or ligand binding by proteins. Still, cysteine's unusual biological distribution has remained mysterious, being strikingly underrepresented in transmembrane domains and on accessible protein surfaces, particularly in aerobic life forms ("cysteine anomaly"). Noting that lipophilic thiols have been used for decades as radical chain transfer agents in polymer chemistry, we speculated that the rapid formation of thiyl radicals in hydrophobic phases might provide a rationale for the cysteine anomaly. Hence, we have investigated the effects of dodecylthiol and related compounds in isolated biomembranes, cultivated human cells and whole animals (C. elegans). We have found that lipophilic thiols at micromolar concentrations were efficient accelerators, but not inducers of lipid peroxidation, catalyzed fatty acid isomerization to trans-fatty acids, and evoked a massive cellular stress response related to protein and DNA damage. These effects were specific for lipophilic thiols and were absent with thioethers, alcohols or hydrophilic compounds. Catalytic chain transfer activity by thiyl radicals appears to have deeply influenced the structural biology of life as reflected in the cysteine anomaly. Chain transfer agents represent a novel class of biological cytotoxins that selectively accelerate oxidative damage in vivo.

High-Risk Atherosclerosis and Metabolic Phenotype: The Roles of Ectopic Adiposity, Atherogenic Dyslipidemia, and Inflammation.

Current algorithms for assessing risk of atherosclerotic cardiovascular disease (ASCVD) and, in particular, the reliance on low-density lipoprotein (LDL) cholesterol in conditions where this measurement is discordant with apoB and LDL-particle concentrations fail to identify a sizeable part of the population at high risk for adverse cardiovascular events. This results in missed opportunities for ASCVD prevention, most notably in those with metabolic syndrome, prediabetes, and diabetes. There is substantial evidence that accumulation of ectopic fat and associated metabolic traits are markers for and pathogenic components of high-risk atherosclerosis. Conceptually, the subset of advanced lesions in high-risk atherosclerosis that triggers vascular complications is closely related to a set of coordinated high-risk traits clustering around a distinct metabolic phenotype. A key feature of this phenotype is accumulation of ectopic fat, which, coupled with age-related muscle loss, creates a milieu conducive for the development of ASCVD: atherogenic dyslipidemia, nonresolving inflammation, endothelial dysfunction, hyperinsulinemia, and impaired fibrinolysis. Sustained vascular inflammation, a hallmark of high-risk atherosclerosis, impairs plaque stabilization in this phenotype. This review describes how metabolic and inflammatory processes that are promoted in large measure by ectopic adiposity, as opposed to subcutaneous adipose tissue, relate to the pathogenesis of high-risk atherosclerosis. Clinical biomarkers indicative of these processes provide incremental information to standard risk factor algorithms and advanced lipid testing identifies atherogenic lipoprotein patterns that are below the discrimination level of standard lipid testing. This has the potential to enable improved identification of high-risk patients who are candidates for therapeutic interventions aimed at prevention of ASCVD.

Effect of 1 Year Krill Oil Supplementation on Cognitive Achievement of Dutch Adolescents: A Double-Blind Randomized Controlled Trial.

Long-chain polyunsaturated fatty acids (LCPUFA) are important for brain development and function, maybe especially during adolescence. Observational studies have demonstrated an association between fish consumption (a source of LCPUFA) and cognition in adolescents, but intervention trials are lacking. The goal of the current study was to investigate the effect of one year of krill oil (a source of LCPUFA) supplementation on the cognitive performance of adolescents with a low Omega-3 Index (O3I ≤ 5%). A double-blind, randomized, and placebo-controlled supplementation trial with repeated measurements (baseline (T0), three months (T1), six months (T2), and 12 months (T3)) in adolescents (267 randomized) was executed. Participants were randomized to 400 mg eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) per day in Cohort I or placebo and 800 mg EPA + DHA per day in Cohort II or placebo. O3I was monitored by a finger prick at all time points. At T0, T2, and T3, participants executed a neurocognitive test battery. Covariate corrected mixed models were run with either condition (krill or placebo) or O3I as predictors. Krill oil supplementation led to a small but significant increase in mean O3I, but few participants increased to the intended O3I range (8-11%). There was no significant effect of supplementation on the neurocognitive tests, nor a relationship between O3I and neurocognitive test scores. The increase in O3I was small in most participants, probably due to non-compliance. Possibly the increase in O3I was too small to demonstrate an effect. More research on the influence of LCPUFAs on cognition in adolescents is needed.

The omega-3 index in patients with heart failure: A prospective cohort study.

BACKGROUND: Epidemiologic studies on the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in heart failure are scarce, while one large intervention trial demonstrated a modest benefit. METHODS: This is a secondary analysis from the Interdisciplinary Network Heart Failure (INH) program. Patients hospitalized for systolic heart failure were enrolled and followed for 36 months. At baseline, whole blood samples from 899 patients were analyzed for fatty acid composition using a standardized analytical procedure (HS-Omega-3 Index®, O3-I). Associations of the O3-I with markers of heart failure severity, clinical characteristics, biomarkers, and mortality were analyzed. RESULTS: The mean O3-I was 3.7 ±â€¯1.0%. Patient mean age was 68 ±â€¯12 years (72% male, 43% in New York Heart Association (NYHA) class III or IV, mean LVEF 30 ±â€¯8%). During follow-up 258 patients (28.7%) died. After adjustment for potential confounders, the O3-I showed weak associations with uncured malignancy, end-systolic diameter of the left atrium, left ventricular end-diastolic and end-systolic diameters, and blood lipids and other laboratory parameters (all p < 0.05), but not with NYHA class, left ventricular ejection fraction, and the underlying cause of heart failure. The O3-I did not predict the 3-year mortality risk. CONCLUSIONS: Our results show a marked depletion of omega-3 fatty acids in patients hospitalized for decompensated heart failure (suggested target range 8-11%). Although the O3-I was associated with a panel of established risk indicators in heart failure, it did not predict mortality risk. CLINICAL TRIAL REGISTRATION: www.controlled-trials.com; ISRCTN23325295.

Low omega-3 index and polyunsaturated fatty acid status in patients with chronic fatigue syndrome/myalgic encephalomyelitis.

BACKGROUND: Several studies have suggested that low levels of omega-3 fatty acids (n-3 PUFAs) including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are associated with cardiovascular risk, major depression, sleep problems, inflammation and other health-related issues. So far, however, erythrocyte PUFA status in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) has not been established. This study aimed to determine whether n-3 PUFA content and omega-3 index are associated with measures in CFS/ME patients. PATIENTS AND METHODS: PUFA levels and omega-3 index were measured in 31 Spanish CFS/ME patients using the HS-Omega-3 Index method. Demographic and clinical characteristics and self-reported outcome measures were also recorded. RESULTS: A low mean omega-3 index (5.75%) was observed in 92.6% of the sample. Omega-3 index was inversely correlated with the AA/EPA ratio (p = 0.00002) and the BMI (p = 0.0106). In contrast, the AA/EPA ratio was positively associated with the BMI (p = 0.0038). No association for FIS-40 and PSQI measures was found (p > 0.05). CONCLUSION: The low omega-3 index found in our CFS/ME patients may indicate increased risks for cardiovascular health, which should be further investigated. A low omega-3 index also suggests a pro-inflammatory state in these patients. Attempts should be made to increase the omega-3 index in CFS/ME patients, based on intervention trials assessing a potential therapeutic value.

Omega-3 Index and Obstructive Sleep Apnea: A Cross-Sectional Study.

STUDY OBJECTIVES: Erythrocyte levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (Omega-3 Index) were previously found to be associated with obstructive sleep apnea (OSA) at very low levels (< 5.0%) in only one epidemiologic study. OSA has comorbidities, such as arterial hypertension, heart failure, or major depression, also associated with a low Omega-3 Index. These comorbidities can be improved by increasing intake of EPA and DHA, and thus the Omega-3 Index, preferably to its target range of 8% to 11%. Symptoms of OSA might improve by increasing the Omega-3 Index, but more research is needed. METHODS: In our sleep laboratory, 357 participants with OSA were recruited, and data from 315 participants were evaluated. Three categories of OSA (none/ mild, moderate, severe) were defined based on apnea-hypopnea index. Anthropometrics and lifestyle characteristics (smoking, alcohol, fish intake, omega-3 supplementation) were recorded. Erythrocyte fatty acid compositions were assessed with the HS-Omega-3 Index methodology. RESULTS: The mean Omega-3 Index in all 3 categories of OSA was 5.7%, and no association with OSA was found. There were more male participants with severe OSA (79.7%, P = .042) than females, and participants with severe OSA had a significantly higher body mass index (32.11 ± 6.39 kg/m2, P = .009) than participants with mild or moderate OSA. Lifestyle characteristics were not significantly different. CONCLUSIONS: In contrast to our hypothesis, an Omega-3 Index of 5.7% was not associated with OSA severity. Previously, an Omega-3 Index < 5.0% was associated. Although our results suggest aiming for an Omega-3 Index > 5.7% in an intervention trial with EPA and DHA in OSA, comorbidities of OSA suggest a target range of 8% to 11%.

Recommendations of the Spanish Menopause Society on the consumption of omega-3 polyunsaturated fatty acids by postmenopausal women.

The consumption of long-chain omega-3 polyunsaturated fatty acids (LCO3-PUFAs) has shown a great variety of beneficial effects, including cardiovascular, metabolic and inflammatory effects, which make them interesting for the postmenopausal woman. Because LCO3-PUFAs could be effective and safe during this period, a panel of experts from the Spanish Menopause Society met to establish a set of recommendations for their use in postmenopausal women based on the best available evidence. The decrease in triglycerides is the most consistent effect observed with LCO3-PUFAs (at doses greater than 3g/day). In addition, LCO3-PUFAs have antiarrhythmic effects, reduce blood pressure, improve depressive and psychotic symptoms, and do not increase the risk of cancer. However, further studies are needed to confirm the benefit of LCO3-PUFAs in the relief of menopause symptoms and osteoporosis.

Public health relevance of drug-nutrition interactions.

The public health relevance of drug-nutrition interactions is currently highly undervalued and overlooked. This is particularly the case for elderly persons where multi-morbidity and consequently polypharmacy is very common. Vitamins and other micronutrients have central functions in metabolism, and their interactions with drugs may result in clinically relevant physiological impairments but possibly also in positive effects. On 12 April 2016, the University Medical Center Groningen (The Netherlands), as part of its Healthy Ageing program, organized a workshop on the public health relevance of drug-nutrient interactions. In this meeting, experts in the field presented results from recent studies on interactions between pharmaceuticals and nutrients, and discussed the role of nutrition for elderly, focusing on those persons receiving pharmaceutical treatment. This paper summarizes the proceedings of the symposium and provides an outlook for future research needs and public health measures. Since food, pharma and health are closely interconnected domains, awareness is needed in the medical community about the potential relevance of drug-nutrition interactions. Experts and stakeholders should advocate for the integration of drug-nutrition evaluations in the drug development process. Strategies for the individual patients should be developed, by installing drug review protocols, screening for malnutrition and integrating this topic into the general medical advice.

Incorporation of EPA and DHA into plasma phospholipids in response to different omega-3 fatty acid formulations--a comparative bioavailability study of fish oil vs. krill oil.

BACKGROUND: Bioavailability of omega-3 fatty acids (FA) depends on their chemical form. Superior bioavailability has been suggested for phospholipid (PL) bound omega-3 FA in krill oil, but identical doses of different chemical forms have not been compared. METHODS: In a double-blinded crossover trial, we compared the uptake of three EPA+DHA formulations derived from fish oil (re-esterified triacylglycerides [rTAG], ethyl-esters [EE]) and krill oil (mainly PL). Changes of the FA compositions in plasma PL were used as a proxy for bioavailability. Twelve healthy young men (mean age 31 y) were randomized to 1680 mg EPA+DHA given either as rTAG, EE or krill oil. FA levels in plasma PL were analyzed pre-dose and 2, 4, 6, 8, 24, 48, and 72 h after capsule ingestion. Additionally, the proportion of free EPA and DHA in the applied supplements was analyzed. RESULTS: The highest incorporation of EPA+DHA into plasma PL was provoked by krill oil (mean AUC0-72 h: 80.03 ± 34.71%*h), followed by fish oil rTAG (mean AUC0-72 h: 59.78 ± 36.75%*h) and EE (mean AUC0-72 h: 47.53 ± 38.42%*h). Due to high standard deviation values, there were no significant differences for DHA and the sum of EPA+DHA levels between the three treatments. However, a trend (p = 0.057) was observed for the differences in EPA bioavailability. Statistical pair-wise group comparison's revealed a trend (p = 0.086) between rTAG and krill oil. FA analysis of the supplements showed that the krill oil sample contained 22% of the total EPA amount as free EPA and 21% of the total DHA amount as free DHA, while the two fish oil samples did not contain any free FA. CONCLUSION: Further studies with a larger sample size carried out over a longer period are needed to substantiate our findings and to determine differences in EPA+DHA bioavailability between three common chemical forms of LC n-3 FA (rTAG, EE and krill oil). The unexpected high content of free EPA and DHA in krill oil, which might have a significant influence on the availability of EPA+DHA from krill oil, should be investigated in more depth and taken into consideration in future trials.

Major depressive disorder is associated with cardiovascular risk factors and low Omega-3 Index.

OBJECTIVE: Cardiovascular disease (CVD) and major depressive disorder (MDD) are frequent worldwide and have a high comorbidity rate. Omega-3 fatty acids have been suggested as disease modulators for both CVD and MDD. Therefore, we studied whether polyunsaturated fatty acids and the Omega-3 Index may represent markers for assessment of the cardiovascular risk in somatically healthy patients suffering from MDD. METHOD: We conducted a case-control study from July 2004 to December 2007 in 166 adults (86 inpatients with MDD but without CVD from the Department of Psychiatry and Psychotherapy and 80 age- and sex-matched healthy controls from an outpatient clinic of the Division of Preventive Cardiology, Ludwig Maximilian University of Munich, Germany). Information gathered at baseline included MDD diagnosis according to DSM-IV criteria, depression ratings, conventional cardiovascular risk factors, and fatty acid and interleukin-6 determinations. Fatty acid composition was analyzed according to the HS-Omega-3 Index methodology. During the study, patients received no supplementation with omega-3 fatty acids. The main inclusion criteria were the diagnosis of MDD according to DSM-IV and a 17-item Hamilton Depression Rating Scale (HDRS-17) score of at least 17. Treatment response and remission were defined using the HDRS-17. RESULTS: Several conventional risk factors such as high triglyceride (mean, 152 mg/dL vs 100 mg/dL; P < .001) and fasting glucose (mean, 96 mg/dL vs 87 mg/dL; P = .005) values as well as greater waist circumference (mean, 97 cm vs 87 cm; P = .019) and higher body mass index (calculated as kg/m(2); mean, 26 vs 24; P = .011) were more prevalent in MDD patients in comparison with controls. The Omega-3 Index (mean, 3.9% vs 5.1%; P < .001) and individual omega-3 fatty acids were significantly lower in MDD patients. An Omega-3 Index < 4% was associated with high concentrations of the proinflammatory cytokine interleukin-6 (χ(2) = 7.8, P = .02). CONCLUSIONS: Conventional cardiovascular risk factors, the Omega-3 Index, and interleukin-6 levels indicated an elevated cardiovascular risk profile in MDD patients currently free of CVD. Our results support the employment of strategies to reduce the cardiovascular risk in still cardiovascularly healthy MDD patients by targeting conventional risk factors and the Omega-3 Index.

Coronary artery disease.

SUMMARY: Prevention is equivalent to causal treatment of cardiovascular disease. Nowadays, guidelines are elaborated on the basis of large-scale long-term intervention studies and structured meta-analyses. This review attempts a synopsis of guidelines of the American and German Heart Associations. For secondary prevention, smoking cessation, blood pressure treatment, dietary lipid management, aerobic activity, correct body weight, Mediterranean diet, treatment of diabetes to a HbA1c of 7%, ingestion of marine w-3 fatty acids (1 g / day), platelet inhibitors, lipid-lowering agents (statins), beta-blockers and ACE-inhibitors are established. In primary prevention pharmaceutical agents are not incorporated, but all non-pharmacological approaches are being recommended. The guidelines mentioned are based on unequivocal evidence, risk-benefit and cost-benefit ratios are good, nevertheless implementation remains a serious problem. Primary and secondary prevention are already giving way to risk-adapted prevention, based on an individual assessment of a person's cardiovascular risk.

The effect of 17beta-estradiol on endothelial and inflammatory markers in postmenopausal women: a randomized, controlled trial.

BACKGROUND: Intervention trials in postmenopausal women with coronary artery disease have failed to demonstrate beneficial effects of hormone replacement therapy (HRT) on the course of disease, potentially due to pro-inflammatory effects of conjugated equine estrogens. We characterized the effects of 48 weeks treatment with two estradiol-based HRT regimens on nonspecific (high sensitivity C-reactive protein [hs-CRP], blood sedimentation rate [BSR], fibrinogen) and specific endothelial markers (cell adhesion molecules: ICAM-1, VCAM-1, E-selectin). METHOD AND RESULTS: Postmenopausal women randomly received either 1 mg 17beta-estradiol daily plus 25 microg gestodene for the last 12 days of each 28 day cycle (=standard dose progestin; n=65), or gestodene added each third cycle only (=low dose progestin; n=65), or no HRT (n=73). Both HRT regimens reduced levels of ICAM-1 (-9%), VCAM-1 (-9%), E-selectin (-11%), fibrinogen (-12%), BSR (-5%). No effect was observed on hs-CRP levels in any group. In smokers, E-selectin remained unchanged whereas ICAM-1 and VCAM-1 were lowered. Subjects on antihypertensive or lipid lowering medication showed effects comparable to the whole cohort. Effects of low and standard dose progestin were not different. CONCLUSION: We conclude that a combination therapy with 1 mg 17beta-estradiol favourably affects the vascular inflammation processes as indicated by a neutral effect on hs-CRP and reduction of cell adhesion molecules.

Effect of postmenopausal hormone replacement on atherosclerosis in femoral arteries.

OBJECTIVES: On the basis of epidemiological and experimental data, it has been supposed that hormone replacement therapy (HRT) inhibits atherosclerosis in postmenopausal women. This randomized controlled trial examined whether 1 mg 17beta-estradiol daily, combined cyclically with 0.025 mg gestodene in every month (HRT 1), or in every third month (HRT 2) slows the increase of intima-media thickness in femoral arteries compared with no HRT. METHODS: Healthy postmenopausal women (n=321) with an increased risk for future vascular disease as indicated by >1 mm of intima-media thickness in the carotid arteries were equally randomized to one of the three groups for 48 weeks. Ultrasound scans of femoral arteries were recorded at study start and study end, together with a thorough clinical examination and laboratory work-up. RESULTS: Complete scans were obtained in 260 of the 264 subjects who participated until study end. Mean maximum intima-media thickness of four femoral artery segments (common and superficial, both sides) was 0.93+/-0.37 mm (mean+/-S.D.) at study start. It increased by 0.02+/-0.05, 0.02+/-0.05, and 0.03+/-0.05 mm in the HRT 1, HRT 2 and no HRT groups, respectively (HRT 1 versus no HRT, HRT 2 versus no HRT; both P>0.2). Compared with no HRT, HRT significantly lowered follicle stimulating hormone, low-density lipoprotein cholesterol, and fibrinogen. CONCLUSIONS: In this 1-year trial, irrespective of the progestogen dose used, HRT with 1 mg 17 beta-estradiol did not inhibit progression of femoral artery atheroslerosis in postmenopausal women with subclinical vascular disease.